Subiculm circuits for cortical feedback regulation of spatial mapping and learning

用于空间映射和学习的皮层反馈调节的下电路

基本信息

批准号：
10318631
负责人：
Douglas Arthur Nitz
金额：
$ 50.28万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-12-15 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10318631
关键词：
Address Affect Alzheimer&apos s Disease Anatomy Animal Model Animals Back Behavior Behavioral Brain Brain region Calcium Canine Adenoviruses Cells Cognition Complex Data Decision Making Environment Etiology Exhibits Feedback Genetic Goals Hippocampal Formation Hippocampus (Brain)Image Label Learning Left Link Location Mammals Maps Medial Mediating Memory Mus Neurons Output Parietal Lobe Pathway interactions Pattern Performance Physiological Play Population Positioning Attribute Process Property Publishing Rattus Regulation Reporting Research Resolution Role Route Running Specific qualifier value Structure Synapses System Temporal Lobe Epilepsy Testing Time Travel Viral Visual Cortex base combinatorial designer receptors exclusively activated by designer drugs entorhinal cortex genetic approach genetic manipulation hippocampal subregions human model in vivo insight microscopic imaging neocortical nervous system disorder neural circuit neural correlate neurophysiology novel optogenetics rabies viral tracing relating to nervous system spatial relationship vector virus genetics way finding

项目摘要

Project Summary / Abstract Encoding of environmental location and navigational behavior in mammals involves large ensembles of specific neuron types across multiple interacting brain regions. “Place cell” and “grid cell” mapping of spatial location in the CA1 region of hippocampus and medial entorhinal cortex (EC), respectively, is thought to be fed forward to associative cortical brain regions including the posterior parietal cortex (PPC) and retrosplenial cortex (RSP) to map conjunctions of egocentric and external spatial relationships. This notion implies that the hippocampal-neocortical pathway involves a gradual transformation of spatial cognition to action along with encoding of specific route information at intermediate processing stages. While the characterization of this hippocampal feedforward output to the neocortical system has been conceptually useful for our understanding of spatial navigation processes, it is now time to consider the role of the largely unexplored “top-down” neocortical inputs from RSP to the hippocampus. The subiculum (SUB) is an under-investigated brain structure well positioned to mediate circuit interactions between the hippocampal and neocortical systems. Based on our recent discoveries, we hypothesize that specific subsets of SUB neurons receive significant direct “top-down” inputs from RSP and that these inputs yield specialized SUB encoding of multiple spatial relationships including the axis of travel, boundary vectors, and route sub-spaces. These SUB neurons are expected to overlap with the population of CA1-projecting SUB neurons that exert direct feedback regulation of hippocampus-associated spatial mapping and learning. We propose to study the synaptic circuit organization and functional implications of this “top-down” pathway from RSP cortex, to SUB, to hippocampal CA1, using recent technological advancements. To test the hypothesis, in Aim 1, we will map brain-wide circuit input connections of CA1-projecting SUB neurons and compare these to EC-projecting, and RSP-projecting SUB neurons using new viral tracing and optogenetic stimulation mapping. A combinatorial viral and genetic strategy will be used to selectively label projection-specific SUB neurons for circuit studies and physiological characterization. In Aims 2 and 3, we will link circuit connection mapping to neurophysiological function and behavior. Tetrode recordings and in vivo GCaMP6-based calcium imaging of CA1 at single-cell resolution in freely moving animals will resolve how RSP inputs and projection-specific SUB neurons modulate CA1 place cell activities and how they contribute to spatial learning and navigation. The studies will be conducted in conjunction with behavioral analyses addressing how animals learn object-place associations and routes through environments having multiple interconnected pathways. Genetically targeted neuronal inactivation will be used to establish the causality of circuit connections and function. The proposed studies are aligned with the specified goals of Targeted Brain Circuits Projects, and will contribute to a mechanistic understanding of how dynamic patterns of specific SUB neural activity are transformed into spatial navigation and cognition.

项目概要/摘要哺乳动物的环境位置和导航行为的编码涉及大量的集合跨多个大脑相互作用区域的特定神经元类型的空间映射“位置细胞”和“网格细胞”。分别位于海马 CA1 区和内侧内嗅皮层 (EC) 的位置，被认为是进食的前向关联皮质大脑区域，包括后顶叶皮质 (PPC) 和压后皮质皮质（RSP）来映射自我中心和外部空间关系的连接。海马-新皮质通路涉及空间认知到行动的逐渐转变以及在中间处理阶段对特定路线信息进行编码，同时表征这一点。海马向新皮质系统的前馈输出在概念上对我们的理解很有用在空间导航过程中，现在是时候考虑基本上未被探索的“自上而下”的作用了从 RSP 到海马体的新皮质输入下托 (SUB) 是一个尚未得到充分研究的大脑。结构很好地介导海马和新皮质系统之间的回路相互作用。根据我们最近的发现，我们发现 SUB 神经元的特定子集接收到显着的信号。来自 RSP 的直接“自上而下”输入，这些输入产生多空间编码的专门 SUB 编码这些 SUB 神经元之间的关系包括行进轴、边界向量和路线子空间。预计与 CA1 投射 SUB 神经元群体重叠，这些神经元对我们建议研究海马体相关的空间映射和学习。以及这种从 RSP 皮层到 SUB、到海马 CA1 的“自上而下”通路的功能含义，使用为了检验这一假设，在目标 1 中，我们将绘制全脑电路输入图。 CA1 投射 SUB 神经元的连接，并将它们与 EC 投射和 RSP 投射 SUB 进行比较使用新的病毒追踪和光遗传学刺激映射的神经元。策略将用于选择性地标记投射特异性 SUB 神经元，用于电路研究和生理学在目标 2 和 3 中，我们将把电路连接映射与神经生理功能联系起来。 Tetrode 记录和基于 GCaMP6 的 CA1 单细胞分辨率体内钙成像。自由活动的动物将解决 RSP 输入和投射特异性 SUB 神经元如何调节 CA1 位置的问题细胞活动以及它们如何促进空间学习和导航。与行为分析相结合，研究动物如何学习物体与地点的关联和路线通过具有多个相互关联的途径的环境将导致神经失活。用于建立电路连接和功能的因果关系。所提出的研究与目标脑回路项目的具体目标，并将有助于对特定 SUB 神经活动的动态模式如何转化为空间导航和认知。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Beyond t test and ANOVA: applications of mixed-effects models for more rigorous statistical analysis in neuroscience research.

DOI：
10.1016/j.neuron.2021.10.030
发表时间：
2022-01-05
期刊：
Neuron
影响因子：
16.2
作者：
Yu Z;Guindani M;Grieco SF;Chen L;Holmes TC;Xu X
通讯作者：
Xu X

Adaptive integration of self-motion and goals in posterior parietal cortex.

DOI：
10.1016/j.celrep.2022.110504
发表时间：
2022-03-08
期刊：
CELL REPORTS
影响因子：
8.8
作者：
Alexander, Andrew S.;Tung, Janet C.;Chapman, G. William;Conner, Allison M.;Shelley, Laura E.;Hasselmo, Michael E.;Nitz, Douglas A.
通讯作者：
Nitz, Douglas A.

Longitudinal dynamics of microvascular recovery after acquired cortical injury.

DOI：
10.1186/s40478-022-01361-4
发表时间：
2022-04-25
期刊：
ACTA NEUROPATHOLOGICA COMMUNICATIONS
影响因子：
7.1
作者：
Lin, Xiaoxiao;Chen, Lujia;Jullienne, Amandine;Zhang, Hai;Salehi, Arjang;Hamer, Mary;C. Holmes, Todd;Obenaus, Andre;Xu, Xiangmin
通讯作者：
Xu, Xiangmin

Hippocampal neural circuit connectivity alterations in an Alzheimer's disease mouse model revealed by monosynaptic rabies virus tracing.

DOI：
10.1016/j.nbd.2022.105820
发表时间：
2022-10-01
期刊：
NEUROBIOLOGY OF DISEASE
影响因子：
6.1
作者：
Ye, Qiao;Gast, Gocylen;Su, Xilin;Saito, Takashi;Saido, Takaomi C.;Holmes, Todd C.;Xu, Xiangmin
通讯作者：
Xu, Xiangmin

Inferring neuron-neuron communications from single-cell transcriptomics through NeuronChat.

通过 NeuronChat 从单细胞转录组学推断神经元间通讯。